| First Author | Wan CK | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 7988 | PubMed ID | 26269257 |
| Mgi Jnum | J:224993 | Mgi Id | MGI:5689945 |
| Doi | 10.1038/ncomms8988 | Citation | Wan CK, et al. (2015) IL-21-mediated non-canonical pathway for IL-1beta production in conventional dendritic cells. Nat Commun 6:7988 |
| abstractText | The canonical pathway for IL-1beta production requires TLR-mediated NF-kappaB-dependent Il1b gene induction, followed by caspase-containing inflammasome-mediated processing of pro-IL-1beta. Here we show that IL-21 unexpectedly induces IL-1beta production in conventional dendritic cells (cDCs) via a STAT3-dependent but NF-kappaB-independent pathway. IL-21 does not induce Il1b expression in CD4(+) T cells, with differential histone marks present in these cells versus cDCs. IL-21-induced IL-1beta processing in cDCs does not require caspase-1 or caspase-8 but depends on IL-21-mediated death and activation of serine protease(s). Moreover, STAT3-dependent IL-1beta expression in cDCs at least partially explains the IL-21-mediated pathologic response occurring during infection with pneumonia virus of mice. These results demonstrate lineage-restricted IL-21-induced IL-1beta via a non-canonical pathway and provide evidence for its importance in vivo. |
